IL-18 is a type of cytokine or substance that mediates signal transduction in the immune system. As seen in Japanese Patent Kokai Nos.27,189/96 and 193,098/96 and Okamura et al., Nature, Vol. 378, No. 6,552, pp. 88-91 (1995), IL-18 was provisionally designated as “interferon-gamma inducing factor” immediately after its discovery. This designation was later changed into “IL-18” in accordance with the proposal in Ushio, et al., Journal of Immunology, Vol. 156, pp. 4,274-4,279 (1996). IL-18 in its mature form consists of 157 amino acids. It induces immunocompetent cells in the production of interferon-gamma (hereinafter abbreviated as “IFN-gamma.”), which is a useful biologically-active protein capable of inducing and enhancing the generation and cytotoxicity of killer cells. Extensive research is currently underway to develop and explore the various utility of IL-18 in pharmaceuticals. These greatly expected applications include using IL-18 as antiviral, antimicrobial, antitumor and anti-immunopathic agents.
In nature, cytokines, including IL-18, are produced and secreted as substances responsible for signal transduction in the immune system. Therefore, when cytokines are administered to the body of mammals, they disturb the naturally existing equilibrium in the mammal's immune system. The surfaces of mammalian cells bear sites or “receptors” that are responsible for recognition of cytokines and secreted cytokines transduce no signal in cells until they are bound to the receptors. In a normal immune system, a definite equilibrium exists between respective cytokines and their receptors. There are currently unmet needs in finding and learning the biological and structural properties of IL-18 and its receptors and using such knowledge in designing drugs for treatment and ameliorating diseases and disorders such as viral and microbial infections, cancer, inflammation, etc.